It is well known that both local and volatile anesthetics depress myocardial functions. This study was performed to evaluate the combined effects of commonly utilized local anesthetics (bupivacaine, mepivacaine, and lidocaine) and a volatile anesthetic (isoflurane) on heart rate and myocardial contractility in an isolated rat working heart preparation using each local anesthetic at 0 to 3 x 10(-4) (mol/L) with or without 1 MAC (minimum alveolar concentration) of isoflurane. The three local anesthetics depressed the heart rate and myocardial contractility dose-dependent. Bupivacaine depressed the heart rate more than the other two local anesthetics. One MAC isoflurane showed significant negative inotropic effects, and accelerated the effects of the local anesthetics. By using isobolographic analysis, we concluded that the combined effect of isoflurane and bupivacaine on myocardial negative inotropism was synergistic, while the effects of isoflurane and mepivacaine or lidocaine were additive.